Patrick Daly

AZUHT-PRODUCTIONwarmup

Alkylators, such as cyclophosphamide, are often included in bridging therapy (BT) regimens used to maintain disease control in patients with <a href="https://urbanhealthtoday.com/page/multiple-myeloma">multiple myeloma</a> (MM) undergoing chimeric antigen receptor (CAR) T-cell therapy. To establish optimal cyclophosphamide in BT, researchers compared 3 administrated schedules used at their center: hyperfractionated inpatient regimens, once-weekly outpatient regimens, and non-cyclophosphamide regimens.
Based on their analysis, the researchers reported hyperfractionated administration did not appear to improve disease control. Alternatively, it was associated with longer post-CAR-T infusion platelet count recovery and worse overall survival (OS). Findings from the study were presented in Transplantation and Cellular Therapy.
The <a href="https://www.sciencedirect.com/science/article/abs/pii/S266663672301299X?via%3Dihub" target="_blank" rel="noopener">analysis</a> included 64 unique patients with MM and 70 cases of bridging therapies, of which 29 (41%) included hyperfractionated cyclophosphamide with inpatient dosing every 12-24 hours or as a continuous intravenous infusion, 23 (33%) included weekly cyclophosphamide (as in KPd or KCd), and 18 (26%) did not include cyclophosphamide.
<h3>More Intense Cyclophosphamide Linked to Poorer MM Outcomes</h3>
The report noted that median total concentrations of cyclophosphamide during BT were 2100 mg/m2 in the hyperfractionated group, 615 mg/m2 in the weekly group, and 0 mg/m2 in the non-cyclophosphamide group.
According to the authors, a ≥25% or ≥100 mg/L increase of involved free light chain (iFLC) levels occurred in comparable proportions across groups at 52% for hyperfractionated, 39% for weekly, and 28% for non-cyclophosphamide (P=.25).
In 61 cases of BT that were followed by CAR-T for MM, PFS and neutrophil recovery times were comparable. However, the following outcomes differed by cyclophosphamide intensity:
<table border="1">
<tbody>
<tr>
<td width="156"></td>
<td width="156">Hyperfractioned</td>
<td width="156">Weekly</td>
<td width="156">Non-Cyclophosphamide</td>
</tr>
<tr>
<td width="156">Vein-to-Vein Time</td>
<td width="156">45 days</td>
<td width="156">39 days</td>
<td width="156">46.5 days</td>
</tr>
<tr>
<td width="156">Platelet Recovery Time</td>
<td width="156">64 days</td>
<td width="156">42 days</td>
<td width="156">12 days</td>
</tr>
<tr>
<td width="156">Median OS</td>
<td width="156">15.3 months</td>
<td width="156">30.0 months</td>
<td width="156">Not reached</td>
</tr>
</tbody>
</table>
&nbsp;
The authors summarized, “Given the rarity of objective disease responses to chemotherapy in relapsed/refractory MM our analysis suggests that hyperfractionated [cyclophosphamide] regimens do not outperform once-weekly [cyclophosphamide] regimens for most patients who require BT before CAR-T therapy.”
Related: <a href="http://urbanhealthtoday.com/post/cilta-cel-in-earlier-treatment-lines-for-refractory-multiple-myeloma">Cilta-Cel in Earlier Treatment Lines for Refractory Multiple Myeloma</a>

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